Immunologically-induced glomerulonephritis is felt to be the major cause of renal failure leading to the expensive and less than satisfactory hemodialysis and transplantation therapies currently in use. The studies supported by this project are designed to identify and better understand the immunologic mechanisms responsible for the induction of glomerulonephritis and tubulointerstitial nephritis in man. This is achieved by detailed immunopathologic study of renal tissues and sera submitted to by numerous nephrology and transplant-related nephrology programs throughout the country. Immunopathologic mechanisms can be identified and defined on the basis of the antigen(s) involved. Immunofluorescence studies of renal tissue combined with radioimmunoassays of serum can differentiate antibodies reactive with antigens in or of the glomerulus (for example, the glomerular basement membrane) from the formation and deposition of circulating immune complexes in which the antigen and antibody systems have no relationship to the glomerulus per se. Recently, therapeutic advances have been made in the treatment of these diseases through their early identification and removal of the offending immune mechanisms through immunosuppression and plasmapheresis. Study of the basic immune mechanisms are extended to relevant animal models of experimental nephritis, so that better definition of the pathogenic mechanisms can be gained. In turn, this will give further insight into areas in which manipulation of the immune system or its mediators could lead to therapeutic benefit.